Reviewed, UniProtKB/Swiss-Prot Q9UK32 (KS6A6_HUMAN)

Names and origin

Protein names

Recommended name:
    Ribosomal protein S6 kinase alpha-6
      Short name=S6K-alpha 6
    EC=2.7.11.1
Alternative name(s):
    90 kDa ribosomal protein S6 kinase 6
    p90-RSK 6
    Ribosomal S6 kinase 4
      Short name=RSK-4
    pp90RSK4

Gene names

Name:	RPS6KA6
Synonyms:	RSK4

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	745 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Serine/threonine kinase that may play a role in mediating the growth-factor and stress induced activation of the transcription factor CREB.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated by multiple phosphorylations on threonine and serine residues By similarity.
Subunit structure	Forms a complex with either ERK1 or ERK2 in quiescent cells. Transiently dissociates following mitogenic stimulation By similarity.
Post-translational modification	Autophosphorylated on Ser-389, as part of the activation process By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 2 protein kinase domains.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	central nervous system development Ref.1 Traceable author statement. Source: ProtInc protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro protein kinase cascade Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 745	745	Ribosomal protein S6 kinase alpha-6		PRO_0000086209
Regions
	Domain	73 – 330	258	Protein kinase 1
	Domain	331 – 400	70	AGC-kinase C-terminal
	Domain	426 – 683	258	Protein kinase 2
	Nucleotide binding	79 – 87	9	ATP By similarity
	Nucleotide binding	432 – 440	9	ATP By similarity
Sites
	Active site	198	1	Proton acceptor By similarity
	Active site	543	1	Proton acceptor By similarity
	Binding site	105	1	ATP By similarity
	Binding site	455	1	ATP By similarity
Amino acid modifications
	Modified residue	232	1	Phosphoserine Ref.6
	Modified residue	368	1	Phosphothreonine By similarity
	Modified residue	372	1	Phosphoserine By similarity
	Modified residue	389	1	Phosphoserine By similarity
	Modified residue	581	1	Phosphothreonine By similarity
	Modified residue	742	1	Phosphoserine By similarity
Natural variations
	Natural variant	140	1	Y → C in a lung large cell carcinoma sample; somatic mutation. Ref.7		VAR_040637
	Natural variant	258	1	S → T in a lung adenocarcinoma sample; somatic mutation. Ref.7		VAR_040638
	Natural variant	692	1	D → N: dbSNP rs6616890. Ref.7		VAR_030670
Experimental info
	Sequence conflict	116	1	D → G in CAG38803. Ref.2
	Sequence conflict	295	1	F → L in CAG38803. Ref.2
	Sequence conflict	341	1	R → G in CAG38803. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9UK32-1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 5EC5AB2FA1C19DE8	FASTA	745	83,872
	10 20 30 40 50 60 MLPFAPQDEP WDREMEVFSG GGASSGEVNG LKMVDEPMEE GEADSCHDEG VVKEIPITHH 70 80 90 100 110 120 VKEGYEKADP AQFELLKVLG QGSFGKVFLV RKKTGPDAGQ LYAMKVLKKA SLKVRDRVRT 130 140 150 160 170 180 KMERDILVEV NHPFIVKLHY AFQTEGKLYL ILDFLRGGDV FTRLSKEVLF TEEDVKFYLA 190 200 210 220 230 240 ELALALDHLH QLGIVYRDLK PENILLDEIG HIKLTDFGLS KESVDQEKKA YSFCGTVEYM 250 260 270 280 290 300 APEVVNRRGH SQSADWWSYG VLMFEMLTGT LPFQGKDRNE TMNMILKAKL GMPQFLSAEA 310 320 330 340 350 360 QSLLRMLFKR NPANRLGSEG VEEIKRHLFF ANIDWDKLYK REVQPPFKPA SGKPDDTFCF 370 380 390 400 410 420 DPEFTAKTPK DSPGLPASAN AHQLFKGFSF VATSIAEEYK ITPITSANVL PIVQINGNAA 430 440 450 460 470 480 QFGEVYELKE DIGVGSYSVC KRCIHATTNM EFAVKIIDKS KRDPSEEIEI LMRYGQHPNI 490 500 510 520 530 540 ITLKDVFDDG RYVYLVTDLM KGGELLDRIL KQKCFSEREA SDILYVISKT VDYLHCQGVV 550 560 570 580 590 600 HRDLKPSNIL YMDESASADS IRICDFGFAK QLRGENGLLL TPCYTANFVA PEVLMQQGYD 610 620 630 640 650 660 AACDIWSLGV LFYTMLAGYT PFANGPNDTP EEILLRIGNG KFSLSGGNWD NISDGAKDLL 670 680 690 700 710 720 SHMLHMDPHQ RYTAEQILKH SWITHRDQLP NDQPKRNDVS HVVKGAMVAT YSALTHKTFQ 730 740 PVLEPVAASS LAQRRSMKKR TSTGL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel ribosomal S6-kinase (RSK4; RPS6KA6) is commonly deleted in patients with complex X-linked mental retardation." Yntema H.G., van den Helm B., Kissing J., van Duijnhoven G., Poppelaars F., Chelly J., Moraine C., Fryns J.-P., Hamel B.C.J., Heilbronner H., Pander H.-J., Brunner H.G., Ropers H.-H., Cremers F.P.M., van Bokhoven H. Genomics 62:332-343(1999) [PubMed: 10644430] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232, MASS SPECTROMETRY.
[7]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-140; THR-258 AND ASN-692.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF184965 mRNA. Translation: AAF13190.1. CR536566 mRNA. Translation: CAG38803.1. AK313240 mRNA. Translation: BAG36051.1. AL389887, AL354653 Genomic DNA. Translation: CAC16111.2. AL354653, AL389887 Genomic DNA. Translation: CAD13486.2. CH471104 Genomic DNA. Translation: EAW98575.1.
IPI	IPI00007123.
RefSeq	NP_055311.1.
UniGene	Hs.368153
3D structure databases
HSSP	HSSP built from PDB template 1KWP based on UniProtKB P49137.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UK32. 2 interactions.
STRING	Q9UK32.
PTM databases
PhosphoSite	Q9UK32.
Proteomic databases
PRIDE	Q9UK32.
Genome annotation databases
Ensembl	ENST00000262752; ENSP00000262752; ENSG00000072133; Homo sapiens. [Genome view]
GeneID	27330.
KEGG	hsa:27330.
UCSC	uc004eej.1. human.
Organism-specific databases
CTD	27330.
GeneCards	GC0XM083125.
HGNC	HGNC:10435. RPS6KA6.
HPA	HPA002852. HPA003904.
MIM	300303. gene.
PharmGKB	PA34850.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9UK32.
HOVERGEN	Q9UK32.
OMA	TPITSAN.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
Gene expression databases
ArrayExpress	Q9UK32.
Bgee	Q9UK32.
CleanEx	HS_RPS6KA6.
Genevestigator	Q9UK32.
GermOnline	ENSG00000072133. Homo sapiens.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR017892. Pkinase_C. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR016239. Ribosomal_S6_kinase_II. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Pfam	PF00069. Pkinase. 2 hits. PF00433. Pkinase_C. 1 hit. [Graphical view]
PIRSF	PIRSF000606. Ribsml_S6_kin_2. 1 hit.
ProDom	PD000001. Prot_kinase. 2 hits. [Graphical view] [Entries sharing at least one domain]
SMART	SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 2 hits. [Graphical view]
PROSITE	PS51285. AGC_KINASE_CTER. 1 hit. PS00107. PROTEIN_KINASE_ATP. 2 hits. PS50011. PROTEIN_KINASE_DOM. 2 hits. PS00108. PROTEIN_KINASE_ST. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	50372.
SOURCE	Search...

Entry information

Entry name

KS6A6_HUMAN

Accession

Primary (citable) accession number: Q9UK32
Secondary accession number(s): B2R854 , Q6FHX2, Q8WX28, Q9H4S6

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 1, 2000
Last modified:	November 3, 2009
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.